Acquired immune deficiency syndrome (AIDS) is a diseased induced by HIV. At present, a large number of persons have been infected with this disease. Thus, this disease has been studied widely.
Studies on medicaments for the treatment and prevention of AIDS have been important contents in the research on the treatment of AIDS. In terms of the biological characteristics of HIV, the present studies on anti-HIV medicaments are mainly in the development of effective therapeutic medicaments to the key enzyme during the replication of HIV-HIV reverse transcriptase (HIVRT) and HIV proteinase (HIVPR). The former is also divided into nucleoside HIVRT inhibitors (NRTI) and non-nucleoside HIVRT inhibitors (NNRTI). The main studies are focused on nucleoside analogues, proteinase inhibitors, integrase inhibitors, etc. If reverse transcriptase and proteinase inhibitors are administered for too long time, not only severe toxicity and many complications are caused, but also the patients will generate drug-resistance in vivo, and therapeutic effects are very limited. There is also another important enzyme during HIV replication-integrase, which integrates viral genomes into host cell chromosomes, so that the viruses are incubated in vivo for long term. Integrase is a characteristic enzyme of HIV itself and also an ideal target for designing of anti-HIV drugs. At present, the studies on this aspect are mainly focused on DNA binders and topoisomerase inhibitors, nucleosides, peptides, polyhydroxylated aromatic compounds and so on. However, the structure of HIV integrase has not been clarified yet, and the structure, function and biology of the integrase still have defects. Further, the crystalline structure of total length integrase and the crystalline structure when enzymes bind with inhibitors, with substrate DNA, and with divalent metallic ions have not been known yet. Thus, it is difficult to effectively develop medicaments for the treatment and prevention of AIDS.
Except that the enzyme which is indispensable for self-replication of HIV virus is the action target of anti-HIV drugs, fused proteins of HIV virus are also important action target. The infection of HIV to cells can be inhibited through interception of fusion of HIV virus so as to achieve effective treatment of AIDS. HIV fused protein gp41 is an important ingredient of surface fused proteins of HIV virus and will generate conformational variation during fusion, six bands α-spiral contained in the structure thereof fold to form hairpin structure. Such conformational variation renders that the membrane of viruses and cellular membranes get close to a proper position so as to benefit the carrying out of fusion. Up-to-date study results have shown that if the formation of hairpin structure of HIV fused protein gp41 can be inhibited effectively, the fusion of HIV to cellular membranes can be also prevented.
Therefore, it is possible to develop the research of HIV fused protein inhibitors based on the formation sites of gp41 hairpin structure. The inhibition of HIV membrane fusion can achieved by developing inhibitors to intercept the formation of the hairpin structure so as to finally realize the effective treatment of AIDS.